Hand, foot, and mouth disease (HFMD) demonstrates distinct seasonal patterns in high-incidence regions, highlighting the growing interest in the relationship between meteorological factors and disease transmission. Nevertheless, findings across different geographic areas remain highly heterogeneous. Data on HFMD cases in Zhengzhou City from 2009 to 2023 were obtained from the Zhengzhou Center for Disease Control and Prevention, while meteorological data were sourced from the National Meteorological Data Sharing Service System. Distributed lag nonlinear models (DLNM) was employed to quantify the effects of meteorological variables and extreme weather events on HFMD incidence, as well as to evaluate the impact of various lag periods. DLNM analysis revealed nonlinear exposure–response relationships between HFMD risk with daily mean temperature, relative humidity, and atmospheric pressure. Extreme weather events further elevated the risk. Daily mean temperature demonstrated the peaking relative risk (RR) at 27 °C (RR = 1.17, 95% CI: 1.007–2.349), while relative humidity at 83% corresponded to the highest RR (RR = 1.07, 95% CI: 1.021–1.121). Atmospheric pressure exhibited maximal risk at 1044 hPa (RR = 1.53, 95% CI: 1.014–2.293). These conditions correspond to the higher end of the local climatic distribution, suggesting that HFMD risk increases under relatively warm, humid, and high-pressure conditions. Meteorological factors, including daily average temperature, relative humidity, atmospheric pressure, and extreme weather events, are associated with altered HFMD incidence in Zhengzhou through nonlinear and lagged relationships. These findings provide scientific evidence for early warning systems and targeted public health interventions based on weather forecasts.

ABSTRACT Platelets are crucial to the development of thrombosis and coagulation abnormalities in sepsis, but the mechanisms by which they contribute to these pathological processes are not fully understood. Here, we identify a key role for platelet‐released heat shock protein 90α (HSP90α) in driving neutrophil extracellular trap (NET) formation and supporting thromboinflammation during sepsis. Proteomic analysis of platelets from patients with sepsis showed a significant increase in HSP90α, which we traced back to trafficking pathways originating from megakaryocytes. When activated, platelets translocate HSP90α to their plasma membrane and release it into the extracellular space in both free and exosome‐associated forms. Extracellular HSP90α acts as a damage‐associated molecular pattern that binds to toll‐like receptor 4 (TLR4) on neutrophils. This binding activates a downstream MyD88–Beclin 1 signaling pathway, triggering autophagy and leading to NET formation. Blocking extracellular HSP90α with a neutralizing monoclonal antibody significantly reduced NET formation both in vitro and in vivo, resulting in decreased sepsis‐related thrombosis and inflammation. This platelet–HSP90α–TLR4–autophagy–NET pathway not only deepens our understanding of platelet‐induced immunothrombosis but also suggests potential targets for therapies aimed at reducing coagulation problems and organ failure in septic patients.

Evidence linking sarcopenia to cognitive outcomes is largely cross-sectional; longitudinal studies are limited, and whether biological age acceleration modifies this relationship remains unclear. Data were obtained from the China Health and Retirement Longitudinal Study (CHARLS) spanning 2011–2015. Sarcopenia was identified based on three indicators: appendicular skeletal muscle mass, muscle strength, and physical performance. Cognitive trajectories were evaluated using standardized z-scores for global cognition and individual domains. Biological age was calculated using chronological age, creatinine, glucose, and C-reactive protein. To assess longitudinal associations, linear mixed-effects models with random intercepts and slopes were employed. We further tested for interactions and combined effects involving biological age acceleration. A total of 4,376 participants (mean age: 58.2 years; 52.9

Background The governance of human genetic resources (HGRs) in China has evolved quickly, driven by national security concerns and the rapid expansion of the biotechnology sector. This review examines the resulting legal and policy framework, with a focus on cross-border data transfers and the management of informed consent. Methods Employing a comprehensive search strategy integrated with bibliometric analysis, this study synthesized theoretical and methodological developments in Chinese HGRs management. Literature searches spanned publications across PubMed, Web of Science, CNKI, Wanfang database, official government websites, and Google. Results China's HGRs management has evolved from principle-based legislation to specific administrative regulations. Informed consent has become stricter, with HGRs data classified as sensitive personal information requiring separate consent and the right to withdraw. This orientation enables strict oversight but also defines the limits within which informed consent can function. The number of international cooperation projects declined after 2023 due to refined regulatory classifications and multi-departmental collaboration. HGRs cross-border require a security review and filing by the National Health Commission, with sensitive data subject to additional assessment by the Cyberspace Administration. In contrast, general cross-border flows are primarily managed through security assessments or standard contract filings, with the negative list mechanism and risk-level exemptions being piloted in free trade zones. Conclusion National security and data sovereignty remain central to China's HGR governance, shaping strict oversight while limiting the practical reach of informed consent. Cross-border data sharing continues to face challenges, including regulatory discrepancies, privacy risks that extend beyond de-identification, and technical inconsistencies in data formats and annotation standards. Future progress requires enhanced transparency regarding data usage, improved technical interoperability aligned with domestic security requirements, and stronger international coordination through bilateral agreements.

Autism spectrum disorder is a neurodevelopmental condition typified by difficulties in social interactions, repetitive and restricted behaviour and heightened anxiety. Increasing evidence suggests that oxidative stress and neuroinflammatory processes are crucial in the development of these behavioural abnormalities. Ertugliflozin, a sodium-glucose cotransporter-2 inhibitor approved by the FDA for treating type 2 diabetes mellitus, has also been reported to exert antioxidant and anti-inflammatory effects. BTBR T + Itpr3tf/J (BTBR) mice are widely used as a preclinical model of autism spectrum disorder, as they show core autism-like behavioural features. The present study investigated whether ertugliflozin could ameliorate autism spectrum disorder-like behaviour in BTBR mice and explored the associated mechanisms. It was found that ertugliflozin treatment significantly improved social interaction while reducing repetitive behaviours and anxiety-like responses compared with untreated BTBR mice. Ertugliflozin (20 mg/kg/day), administered orally, reduced neuronal loss in the CA1 region of the hippocampus and the prefrontal cortex. In addition, ertugliflozin reduced oxidative stress, as demonstrated by decreased malondialdehyde levels, restoration of glutathione content and improved activities of superoxide dismutase and catalase. A significant suppression of inflammatory cytokines accompanied these biochemical improvements. Furthermore, ertugliflozin significantly inhibited microglial activation in BTBR mice. Collectively, the findings indicate that ertugliflozin alleviates autism spectrum disorder-like behavioural deficits in BTBR mouse models, at least in part, by reducing oxidative stress and neuroinflammation. This study highlights ertugliflozin as a potential therapeutic candidate for the management of autism spectrum disorder.

Bi-allelic mutations in EEFSEC, a key factor in selenoprotein synthesis, cause a severe human selenopathy characterized by developmental delay, spasticity, and profound cerebellar atrophy. While previous studies in invertebrate models framed this condition as an early-onset neurodegenerative disorder, the contribution of primary developmental defects to the severe brain malformations in patients has remained a critical unanswered question. Here, we address this gap using a zebrafish model of EEFSEC deficiency. We discovered that loss of eefsec function does not impair global somatic growth but instead causes specific and significant hypoplasia of the midbrain and hindbrain-the embryonic precursors to the human cerebellum and brain stem. These structural defects directly correlate with robust behavioral impairments, including diminished locomotion and blunted escape responses, mirroring the severe motor dysfunction in patients. Critically, our findings provide the in vivo evidence from a vertebrate model that this disorder involves a primary neurodevelopmental defect, which underlies the severe brain malformations and creates a structurally vulnerable nervous system. This establishes a developmental basis for understanding this condition. We propose that this initial failure in brain construction, which we term a developmental selenopathy, creates a structurally vulnerable nervous system, providing a plausible mechanistic explanation for the human phenotype and proposing a framework for understanding this devastating condition.

This study aims to provide a comprehensive description of clinical phenotypes in a large clinical cohort of children with sex chromosome aneuploidies (SCAs), presenting predominantly with a male phenotype. We hereby particularly focused on the relationship between the sex chromosome composition and clinical phenotypes. Patients with SCAs were identified from a clinical cohort of 20,226 children who presented with one or more of the following clinical phenotypes: external genital anomalies, intellectual/developmental disabilities, speech delay, seizures, growth failure, or gynecomastia. All individuals underwent diagnostic evaluation via fluorescence in situ hybridization (FISH) or karyotyping. We conducted statistical analysis of demographic characteristics and clinical phenotypes. Correlation between clinical phenotypes and genetic findings was explored and visualized using Locally Weighted Scatterplot Smoothing (LOESS) fitted curves and Negative Binomial Regression model (NBR). 153 individuals (0.76

Enterovirus A71 (EV-A71), a member of the genus Enterovirus within the family Picornaviridae , induces neuroinflammation; however, the underlying mechanisms remain incompletely understood. This study demonstrates that the C5a-C5aR1 axis plays a pivotal role in EV-A71-induced blood-brain barrier (BBB) disruption and neuroinflammation, primarily by regulating neutrophil migration. Using human brain specimens and a mouse model, we observed pronounced inflammatory cell infiltration in the brainstem and BBB disruption following EV-A71 infection. Immunofluorescence analysis revealed robust activation of the C5a-C5aR1 axis in fatal EV-A71 cases. Notably, C5aR1 knockout (KO) mice displayed reduced Evans blue extravasation and preserved tight junction protein expression after infection. Immunopathological examination of fatal human cases further confirmed perivascular neutrophil (CD177⁺) infiltration in the brainstem. Importantly, C5aR1 deficiency significantly attenuated neutrophil accumulation and neutrophil extracellular trap (NET) release. Given that peptidylarginine deiminase 4 (PAD4) is a key enzyme driving NET formation, we generated neutrophil-specific PAD4 knockout mice (PAD4 Ne-KO) by crossing S100A8-Cre and PAD4 fl/fl lines. As anticipated, neutrophil-specific PAD4 deletion or pharmacological NET blockade substantially ameliorated BBB injury and neuroinflammation following EV-A71 infection. Overall, our findings underscore a critical role for the C5a-C5aR1-neutrophil/NETs pathway in EV-A71 encephalitis pathogenesis and support its targeting as a therapeutic strategy for critically ill patients.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by core symptoms including impairments in social behavior and communication. The impaired excitatory and inhibitory signals have been implicated in the pathophysiology of social behavior deficits. Altered calretinin (CR)-containing GABAergic interneurons have been observed in ASD, but their roles and underlying mechanisms remain unveiled. Here, using valproic acid (VPA)-exposed mice for CR-Cre and R26::LS-tdTomato (Ai14) model of ASD, we prove that a decreased number of CR interneurons in the mPFC of an animal model for ASD. Double-staining experiments demonstrated the decreased number of CR interneurons stained for c-Fos. Also, reduction in GCaMP7s fluorescence intensity was elicited in sociability and social novelty preference using in vivo fiber photometry, manifesting VPA-induced suppression of CR-positive cell activation. Additionally, we observed the abnormalities of dendrites in CR interneurons including lower dendritic arbors, decreased dendrite complexity, and spine density, paralleled by abnormal development of spine morphology. Intriguingly, the electrophysiological recordings of tdTomato-labeled interneurons revealed that exposure to VPA depressed intrinsic neuronal excitability by decreasing spontaneous and evoked action potential frequencies. These changes were concomitant with impairments of glutamatergic and GABAergic synaptic transmission of CR interneurons. Strikingly, chemogenetic silencing of mPFC CR-expressing interneurons induced social interaction deficits in mice. These sociability impairments can be rescued by optogenetic activation of CR activity in VPA-exposed mice. Our study indicates that prenatal exposure to VPA induced reduced activities, abnormalities in morphological development, and decreased intrinsic excitability as well as accompanying impaired synaptic transmission of CR interneurons. Our findings provide strong evidence for the notion that the CR interneurons has a critical role in the regulation of social behavior in mice and manifest that CR interneurons dysfunction may be implicated in social impairments in ASD.

BACKGROUND:Vanishing White Matter disease (VWM) is a rare autosomal recessive leukoencephalopathy caused by biallelic variants in any of the five subunits of eukaryotic initiation factor 2B (EIF2B1-5), with varied clinical manifestations, including progressive neurological deterioration, cerebellar ataxia, and white matter abnormalities on MRI. Early and accurate diagnosis is crucial for medical interventions and genetic counseling. METHODS:We aimed to characterize the prevalence and spectrum of pathogenic variants of VWM in the Chinese population through Genetic screening for VWM mutations in 36,820 Chinese newborns from 31 hospitals across 14 provinces using next-generation sequencing. Pathogenic and likely pathogenic variants were identified and classified according to ACMG guidelines. Prevalence rates and variant spectra were analyzed. RESULTS:Among screened newborns, 114 carriers with 36 distinct pathogenic and likely pathogenic variants were identified, including 18 novel variants. The overall carrier frequency was 1 in 323. EIF2B2 showed the highest carrier frequency (1 in 498), with c.254 T > A/p.Val85Glu being a hotspot variant (61/74 carriers, 82.4%). The estimated prevalence rate of VWM in China was 1.12/1,000,000. CONCLUSIONS:This large-scale screening provides valuable insights into the genetic landscape of VWM in the Chinese population, contributing to improved genetic counseling, early diagnosis, and management strategies. These findings contribute to enhancing the understanding and management of VWM in China.

Background Severe hand, foot, and mouth disease (HFMD) poses a substantial threat to pediatric health. Host genetic factors, particularly those involved in complement activation, influence susceptibility to HFMD; however, the contribution of complement gene polymorphisms to disease severity remains unclear. Methods A total of 189 HFMD patients caused by coxsackievirus A6 (CVA6) were enrolled from Henan Children’s Hospital; among them, 94 were classified as severe cases and 95 as mild cases. Genomic DNA was isolated from peripheral blood leukocytes using a modified phenol–chloroform extraction protocol. PCR-RFLP was used for genotyping. Logistic regression assessed SNP associations with severe HFMD risk. Results Significant associations were observed for the following genetic variants between patients with mild and severe disease: Complement 5 (C5) rs3761847 (GA vs. GG: OR = 2.547, 95% CI: 1.084–5.982); C3 rs2250656 (TC vs. TT: OR = 1.850, 95% CI: 1.021–3.351); and complement factor H (CFH) rs1065489 (TT vs. GG: OR = 2.804, 95% CI: 1.164–6.751; GT vs. GG: OR = 2.337, 95% CI: 1.085–5.033). ROC analysis showed that complement-related gene polymorphisms had clinical utility for predicting HFMD severity (AUC = 0.653, 95% CI: 0.575–0.730). Moreover, specific genotypes were associated with changes in laboratory parameters. Conclusion Our results suggest that C5, C3, and CFH variants influence susceptibility to severe CVA6-induced HFMD in Chinese Han children. Complement gene polymorphisms may help clinicians identify children at higher risk.

Enterovirus 71 (EV71) is the principal pathogen linked to severe hand, foot, and mouth disease (HFMD), with its pathogenesis remaining poorly understood. Here, we found that EV71 infection dramatically increases the expression of NEAT1, resulting in the formation of paraspeckles. Notably, NEAT1 specifically enhances IFN-β transcription via the DDX60-IRF7 pathway, thereby promoting host resistance to EV71. Further experiments indicated that NEAT1 serves as a positive feedback for DDX60 signaling. In detail, NEAT1 facilitates the relocation of the paraspeckle protein SFPQ to the paraspeckle. This action alleviates SFPQ's transcriptional repression on DDX60 and MDA5, which collaborate to promote IFN-β transcription. Subsequently, we noted a comparable regulation of NEAT1 in vivo. Importantly, our case-control study found that lower NEAT1-2 expression in peripheral blood leukocytes during early HFMD stages correlates with disease severity. Our findings suggest that NEAT1 serves as an intrinsic anti-EV71 molecule, with reduced levels potentially indicating a poor prognosis.

Amino acid metabolism provides significant insight into the development and prevention of many viral diseases. Therefore, the present study aimed to compare the amino acid profiles of hand, foot, and mouth disease (HFMD) patients with those of healthy individuals and to further reveal the molecular mechanisms of HFMD severity. Using UPLC-MS/MS, we determined the plasma amino acid expression profiles of pediatric patients with HFMD (mild, n = 42; severe, n = 43) and healthy controls (n = 25). Brain tissues from CVA6-infected mice were examined using untargeted metabolomics. Several amino acids were significantly different between the three groups. Pathway analysis revealed that arginine, proline, and tryptophan metabolism are implicated in the pathogenesis of HFMD. A similar arginine depletion was observed in the brain tissues of CVA6-infected mice. Importantly, L-arginine supplementation improved the survival rate of CVA6-infected mice, inhibited virus multiplication, and reduced pathological autophagy associated with mTOR-autophagy pathway in the brain. Collectively, arginine, as the hub amino acid metabolite of the mammalian target of rapamycin (mTOR) signaling pathway affecting autophagy, plays an important role in the pathogenesis of severe HFMD. L-arginine supplementation may serve as a potential therapeutic option for critical patients with HFMD.

Infectious mononucleosis (IM), is mainly caused by the primary infection with Epstein-Barr virus (EBV). Generally, most patients with IM are deemed to have a favorable prognosis, yet a small proportion of children will need hospitalization. This study aimed to explore the epidemiological features of IM among hospitalized children in Henan Province from 2014 to 2023 and forecast monthly IM hospitalizations in 2024. We conducted a retrospective analysis of all inpatients with IM in Henan Children’s Hospital and the Third Affiliated Hospital of Zhengzhou University from January 2014 to December 2023. Demographic information, clinical diagnosis, and admission time were meticulously analyzed. Wavelet analysis and SARIMA model were employed to identify disease periodicity and forecast hospitalization with IM, respectively. There were 7,269 IM inpatients, which accounted for 0.70

Metabolic-associated fatty liver disease (MAFLD) has emerged as a critical pediatric health concern, particularly among children with obesity. However, its diagnosis poses substantial challenges, especially in the use of non-invasive methods. Our goal was to construct an online nomogram for screening MAFLD in obese children. We designed a retrospective cross-sectional study involving 2,512 obese children. Detailed anthropometric data and laboratory parameters were collected. The study dataset was randomly allocated into training (n = 1758) and validation (n = 754) sets at a 7:3 ratio. To identify MAFLD risk factors, we conducted logistic regression analyses, from which a web-based predictive nomogram was constructed. Using receiver operating characteristic (ROC) curves and area under the curve (AUC), the nomogram’s performance was assessed and contrasted with the triglyceride glucose (TyG) index, Zhejiang University (ZJU) index, and Korean NAFLD (K-NAFLD) score. The goodness-of-fit of the nomogram was evaluated using calibration plots, and the nomogram’s clinical value was assessed using decision curve analysis (DCA). A total of 1,344 participants (53.50

Dimethyl phthalate (DMP) has been extensively utilized as a plasticizer on a global scale for many years. Its presence in the environment and its harmful effects on living organisms have raised concerns. This study aimed to examine its potential developmental neurotoxicity by utilizing zebrafish as a model. Zebrafish embryos were exposed to different concentrations of DMP (5-100 mg/L) from 4 to 120 h post-fertilization (hpf). The survival, hatching, and malformation rates were recorded for each group. Behavioral analysis was conducted on zebrafish larvae, and transgenic zebrafish Tg(elavl3:EGFP) were used to assess the impact of DMP on neuronal cells. The mRNA levels of key neurological marker genes were evaluated at 96 hpf of DMP exposure. The study revealed that exposure to DMP resulted in decreased survival and hatching rates in zebrafish. Embryos treated with 50 mg/L of DMP exhibited lower average survival rates (72.78-78.33%) between 24-96 hpf, while treatment with 25-50 mg/L of DMP resulted in reduced hatching rates (39.44% and 2.22%, respectively) at 48 hpf compared to the control group. Moreover, exposure to 25-50 mg/L of DMP caused an increase in malformations, such as tail curvature, spinal curvature, yolk sac edema and pericardial edema. Interestingly, at 24 hpf, DMP also resulted in an increase in spontaneous tail coiling in zebrafish embryos, as well as a decrease in their swimming distance at 120 hpf. Furthermore, treatment with 50 mg/L of DMP led to a decrease in the fluorescence intensity of transgenic zebrafish Tg( elavl3 : EGFP). RT-qPCR analysis showed a significant down-regulation of marker genes ( gap43, mbp, alpha 1-tubulin, syn2a) associated with nervous system function in DMP-treated zebrafish. Overall, these findings offer a thorough understanding of the mechanisms underlying the neurotoxicity caused by DMP, highlighting the risk of DMP on developmental and neurotoxic effects in zebrafish. Therefore, strict supervision of DMP use and release is essential to safeguard ecological and aquatic organisms.

Prenatal alcohol exposure is a leading cause of developmental abnormalities and neurobehavioral deficits, collectively known as fetal alcohol spectrum disorder (FASD). The underlying molecular mechanisms, however, are not fully elucidated, hindering the development of effective therapeutic strategies. Ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation, has emerged as a key pathological process in various diseases. Gastrodin (GAS), the primary bioactive component of Gastrodia elata, has demonstrated potent antioxidant and neuroprotective properties. This study aimed to investigate the protective effects of GAS against alcohol-induced developmental and neurotoxic damage and to elucidate the underlying molecular mechanisms. Using a zebrafish larval model, we found that exposure to 200 mM alcohol from 2 to 24 hours post-fertilization (hpf) induced significant developmental toxicity, including a decreased hatching rate, body length and eye diameter, and increased morphological malformations in larvae. Alcohol-exposed larvae also exhibited severe neurobehavioral deficits, characterized by a reduction in movement distance and average velocity in dark conditions. Mechanistically, alcohol exposure triggered ferroptosis, evidenced by an increase in intracellular Fe2+, malondialdehyde (MDA), and reactive oxygen species (ROS) levels, alongside a decrease in the levels of glutathione (GSH) and reduced glutathione peroxidase 4 (GPX4) and the nuclear factor erythroid 2-related factor 2 (Nrf2) activities. Co-treatment with GAS (200 mg/L) significantly ameliorated these alcohol-induced developmental and neurobehavioral defects. GAS administration effectively suppressed the hallmarks of ferroptosis by restoring the ROS level and altering the expression of genes related to oxidative stress. In addition, GAS suppressed alcohol-induced cell apoptosis, downregulated caspase3b, bax, caspase8, and upregulated bcl2 in mRNA levels. Molecular analysis revealed that GAS exerts its anti-ferroptotic effect by activating Nrf2/GPX4 signaling pathway, which was suppressed by alcohol. Our findings indicate that ferroptosis plays a key role in alcohol-induced developmental neurotoxicity, and GAS provides protection by activating the Nrf2/GPX4 axis. This suggests that GAS could be a potential therapeutic option for reducing the negative effects of prenatal alcohol exposure.

BACKGROUND:Avoidable mortality (AM) refers to deaths preventable through effective prevention measures or timely medical treatment, and reducing AM is crucial for improving child survival rates. We conducted an analysis of the situation and temporal trends of AM among under-five (U5) children in China. METHODS:Data were extracted from the China Death Surveillance Dataset. The Joinpoint regression and multivariate linear regression were used. RESULTS:The AM rate among U5 children decreased from 233.99/100,000 in 2004 to 34.54/100,000 in 2021, with an average annual percentage change of -10.72% (-11.90%, -9.98%). The proportion of AM generally showed a downward trend, with urban-rural disparities observed particularly evident by year-end 2021. Perinatal mortality is declining at an average rate of 9.75% per year, the proportion of perinatal deaths to all deaths has not changed significantly, and even the proportion of deaths caused by birth injury and suffocation has increased (annual percent change: 0.95%, 95% CI:0.39% to 1.59%). For boys and girls aged 1-5 years, the leading causes of death are drowning and land transport accidents, respectively, with the incidence of drowning in rural areas being higher than in urban areas. CONCLUSIONS:China has reduced AM in U5 children, but rural areas still need targeted interventions to address preventable deaths and achieve Sustainable Development Goals. IMPACT:Avoidable mortality among children under-five in China decreased by an average of 10.72% between 2004 and 2021, with urban-rural differences. Perinatal mortality declined by 9.75% annually, but the proportion of perinatal deaths remained stable, while deaths from birth injury and suffocation increased. For boys aged 1-5 years, drowning is the leading avoidable cause of death, while for girls, it is land transport accidents, with drowning more prevalent in rural areas. Increasing health technicians in rural areas may narrow the rural-urban gap, with targeted interventions needed for birth injury and suffocation, drowning, and land transport accidents.

Dysfunction in social interactions is a core symptom of autism spectrum disorder (ASD). Nevertheless, the neural mechanisms underlying social deficits in ASD are poorly understood. By integrating electrophysiological, in vivo fiber photometry, viral-mediated tracing, optogenetic and pharmacological stimulation, we show reduced intrinsic excitability and hypoactivity of SOM interneurons in medial prefrontal cortex (mPFC) in Magel2-deficient mice, an established ASD model, were required to social defects. Chemogenetic inhibition of mPFC SOM-containing interneurons resulted in reduced social interaction in wild-type Magel2 mice. These sociability deficits can be rescued by optogenetic activation by excitability of SOM in the mPFC and mPFCSOM-LS inhibitory pathway in Magel 2 knockout mice. These results demonstrate the hypoactivity for SOM action in the mPFC in social impairments, and suggest targeting this mechanism that may prove therapeutically beneficial for mitigating social behavioral disturbances observed in ASD.

BACKGROUND:Bainbridge-Ropers syndrome (BRPS) is an uncommon genetic disorder characterized by developmental delay, intellectual disability, distinctive facial features, and various congenital anomalies primarily attributed to mutations in the Additional Sex Combs Like 3 (ASXL3) gene. In this case report, we employed Next-Generation Sequencing techniques for genetic analysis to investigate the clinical phenotype, imaging manifestations, and genetic characteristics of BPRS syndrome caused by ASXL3 gene mutation to enhance our understanding of BPRS and its underlying genetic factors. CASE PRESENTATION:This study presents a case of an infant male, aged 4 months and 6 days, who was referred to our hospital with symptoms including fever, cough, and wheezing. The patient had a history of constitutional weakness, previous hospitalizations for respiratory distress, and treatment with continuous positive airway pressure (CPAP). Whole exome sequencing identified a de novo heterozygous ASXL3 gene variant located on chromosome 18 (chr18:31318777-31318779; NM_030632.3; exon 11), described as c.1409_1411delinsTT (p. His470Leufs*14), resulting in a frameshift mutation leading to the diagnosis of BRPS. This variant was classified as pathogenic based on ACMG guidelines. CONCLUSION:To the best of our knowledge, this variant in the patient has not been reported previously in the literature. This study presents a novel case of the ASXL3 gene variant, emphasizing the significance of genetic analysis in patients with complex clinical presentations. Moreover, it underscores the imperative need for further research on the genetic underpinnings of rare diseases.